Ixabepilone in Treating Patients With Recurrent or Persistent Leiomyosarcoma of the Uterus Previously Treated With Chemotherapy

Official Title ICMJE

A Phase II Evaluation of Ixabepilone (NSC #710428) in the Treatment of Recurrent or Persistent Leiomyosarcoma of the Uterus

Brief Summary

This phase II trial is studying the side effects and how well ixabepilone works in treating patients with recurrent or persistent leiomyosarcoma of the uterus previously treated with chemotherapy. Drugs used in chemotherapy, such as ixabepilone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the response rate (complete and partial responses by RECIST 1.1) of ixabepilone in patients with recurrent or persistent leiomyosarcoma of the uterus who have failed one previous chemotherapy regimen.

II. To determine the nature and degree of toxicity of ixabepilone as assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 in this cohort of patients.

SECONDARY OBJECTIVES:

I. To determine the duration of progression-free survival (PFS) and overall survival (OS).

II. To determine the level of beta-III tubulin expression measured by IHC in women with leiomyosarcoma.

III. To determine if beta-III tubulin expression as measured by IHC predicts response to ixabepilone in women with leiomyosarcoma.

OUTLINE:

Patients receive ixabepilone intravenously (IV) over 3 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

* Includes publications given by the data provider as well as publications
identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ICMJE

Active, not recruiting

Enrollment ICMJE

26

Completion Date

Not Provided

Primary Completion Date

July 2014 (final data collection date for primary outcome measure)

Eligibility Criteria ICMJE

Inclusion Criteria:

Histologically confirmed uterine leiomyosarcoma

Persistent or recurrent disease that is refractory to curative or established treatments

Histologic confirmation of the original primary tumor is required

Measurable disease defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded)

Each lesion must be ≥ 10 mm by CT scan, MRI, or caliper measurement by clinical exam OR ≥ 20 mm by chest x-ray

Lymph nodes must be ≥ 15 mm in short axis by CT scan or MRI

Must have ≥ 1 "target lesion" to assess response

Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence ≥ 90 days following completion of radiotherapy

Not eligible for a higher priority GOG protocol, if one exists

Must have had 1 prior cytotoxic regimen that included a taxane regimen for management of leiomyosarcoma

Single-agent or multi-agent therapy allowed

Patients who did not receive prior therapy with a taxane (e.g., docetaxel) must receive a second regimen that includes a taxane

No known brain metastases

GOG performance status 0-2

Life expectancy > 6 months

ANC ≥ 1,500/mm³

Platelet count ≥ 100,000/mm³

Creatinine ≤ 1.5 times upper limit of normal (ULN)

Bilirubin ≤ 1.5 times ULN

AST ≤ 3 times ULN

Alkaline phosphatase ≤ 2.5 times ULN

Peripheral neuropathy (sensory or mother) ≤ grade 1

Negative pregnancy test

Not pregnant or nursing

Fertile patients must use effective contraception prior to and for the duration of study participation

Free of active infection requiring antibiotics

Uncomplicated urinary tract infection allowed

No other invasive malignancy except non-melanoma skin cancer or curatively treated localized cancer of the breast, head and neck, or skin that was completed more than 3 years ago and the patient remains free of recurrence or metastatic disease

No history of a severe hypersensitivity reaction to agents containing Cremophor EL or its derivatives (e.g., polyoxyethylated castor oil)

No uncontrolled intercurrent illness including, but not limited to, any of the following:

Ongoing or active infection

Symptomatic congestive heart failure

Unstable angina

Cardiac arrhythmia

Psychiatric illness and/or social situations that would limit compliance with study requirements

No concurrent amifostine or other protective agents

Recovered from effects of recent surgery, radiotherapy, or chemotherapy

At least 1 week since prior hormonal therapy

Hormonal therapy (cytotoxic or non-cytotoxic) not counted as prior regimen

At least 3 weeks since any other prior therapy directed to the malignant tumor, including immunologic agents

At least 4 weeks since prior radiation therapy

One prior non-cytotoxic (biologic or cytostatic) regimen, administered as part of the previous cytotoxic regimen or in addition to it, allowed

Non-cytotoxic agents include, but are not limited to, the following:

Monoclonal antibodies

Cytokines

Small-molecule inhibitors of signal transduction

More than 3 years since radiotherapy for localized cancer of the breast, head and neck, or skin provided patient remains free of recurrence or metastatic disease

No prior ixabepilone

No prior chemotherapy for any abdominal or pelvic tumor other than for the treatment of uterine leiomyosarcoma within the past 3 years

Prior chemotherapy for localized breast cancer allowed provided it was completed more than 3 years ago and patient remains free of recurrent or metastatic disease